NMP in Relapsed / Refractory Myeloma

NCT02468687 | Completed Phase 1 DMC

• 1 other identifier: HREC/14/MH/159
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate if the N-methyl-pyrrolidone (NMP) can be safely administered to humans at doses, which induce measurable immunological and anti-tumour effects in patients with myeloma who are resistant to or intolerant of lenalidomide and bortezomib.

Conditions

Multiple Myeloma

Keywords

Relapsed/Refractory

Outcome Measures

Primary Outcomes (1)

• Adverse events to establish the Maximum Tolerated Dose (MTD)

  Each patient will be monitored for adverse events during the first cycle of NMP treatment (28 days) to establish the maximum tolerated dose

  28 days

Secondary Outcomes (5)

• Optimum biological dose (OBD)

  6 months

• Safety of the repeated dosing of NMP by oral administration - possible toxicities

  6 months

• Pharmacokinetic properties of NMP after oral administration

  Predose,0.5,1,2,4,8, 24 hours post dose

• Response rate measured using IMWG criteria

  6 months up to 2 years

• Time to progression from start of treatment

  up to 3.5 years

Study Arms (1)

N-methyl-pyrrolidone

OTHER

NMP dose escalation in accelerated phase and standard phase

Drug: N-methyl-pyrrolidone

Interventions

N-methyl-pyrrolidone DRUG

NMP will be taken each morning as a single daily dose of oral suspension at a concentration of 50mg/ml on an empty stomach at least 30 minutes prior to food.

Also known as: NMP

N-methyl-pyrrolidone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of plasma cell myeloma defined by WHO 2008 criteria
• Measurable disease as defined by at least one of:
• serum M protein ≥5g/L
• urine M protein ≥ 200mg/24hrs
• involved serum free light chain ≥ 100mg/L
• measurable (by imaging at the discretion of the investigator) soft tissue plasmacytoma
• Relapsed, refractory or intolerant of both bortezomib and lenalidomide
• Definitions:
• refractory at least 4 weeks of therapy administered, with less than a partial response by IMWG criteria
• relapsed from previous response (PR or greater) to therapy, with subsequent disease progression as defined as development of bone marrow dysfunction (fall in Hb of 20g/L or platelet count \<100 x 109/L) due to increased bone marrow plasmacytosis
• OR new lytic bone lesions
• OR increase in serum M protein of 5g/L
• OR absolute increase of involved serum free light chain of \>250mg/L
• intolerant: grade 2 or higher toxicity unresponsive to dose adjustment 4. Prior autologous stem cell transplant, unless ineligible for transplant by the discretion of the investigator.
• \. age ≥18 years 6. ECOG performance status \<2 7. The following values within 7 days of commencing NMP (blood transfusions prior to study entry are permitted)

You may not qualify if:

• Pregnant or breastfeeding female patients
• Female of child bearing potential unwilling or unable to use two methods of contraception
• Received chemotherapy, immunotherapy or biological therapy within two weeks of enrolment. Prednisolone up to 20mg per day permitted for non-myeloma indications.
• Patients with a history of another malignancy within 2 years of the baseline visit, excluding treated non-melanotic skin cancer and in-situ carcinoma.
• Patients with known CNS involvement unless previously treated and well controlled for a period of ≥3 months AND which do not require the use of steroids.
• Uncontrolled intercurrent illness including, but not limited to:
• Active or uncontrolled infection, including active HIV or viral (A, B or C) hepatitis. NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible i.e. the patient should be afebrile for at least 72 hours and be haemodynamically stable.
• Impaired cardiac function, including any of the following:
• Myocardial infarction within previous 3 months prior to starting study
• Symptomatic congestive heart failure (New York Heart Association Class III, IV)
• Symptomatic coronary artery disease
• Cardiac arrhythmia not controlled by medication
• Clinically significant resting bradycardia (\<50 beats per minute)
• Long QT syndrome or a known family history of long QT syndrome or QTc \> 450 msec on baseline ECG (using the QTcF formula). If QTcF \>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
• Inability to monitor the QT/QTc interval on ECG

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• Melbourne Health: collaborator

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

N-methylpyrrolidone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David Ritchie, Prof

  Melbourne Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2015
• First Posted: June 11, 2015
• Study Start: August 20, 2015
• Primary Completion: October 7, 2021
• Study Completion: October 7, 2021
• Last Updated: May 5, 2022

Record last verified: 2022-05

Locations

AU (1)